Integration of metabolism Flashcards

1
Q

What can the brain NOT metabolise?

A

Fatty acids

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2
Q

What can partially substitute for glucose in the brain?

A

Ketone bodies

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3
Q

At what concentration is blood glucose conc. in the liver kept at?

A

4 - 5.5 mM

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4
Q

What energy sources do muscles and the heart use?

A

carbohydrate and fatty acid metabolism

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5
Q

What can pyruvate and other TCA cycle intermediates be a source of?

A

Amino acids

Backbone of this molecule can be used to make nucleotides

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6
Q

What can be used as a source of nucleotide production?

A

Glucose-6-phosphate via pentose phosphate pathway.

Generates bulk NADH needed for anabolic pathways

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7
Q

What levels of blood glucose leads to a hypoglycaemia coma?

A

Levels below 30mM

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8
Q

What short term things does the body do to avoid hypoglycaemia?

A

Break down glycogen stores in liver
Release free fatty acids from adipose tissues
Convert acetyl CoA into ketone bodies via liver

These effects only last 12-18 hours so gluconeogenesis pathway used to make more glucose

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9
Q

What is the aim of gluconeogenesis?

A

Avoid hypoglycaemia by producing glucose from pyruvate/ oxaloacetate

Pyruvate can be converted to oxaloacetate by pyruvate carboxylase or converted to acetyl CoA which enters TCA cycle

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10
Q

Whats distinct about reactions that are catalysed by kinases in glycolysis?

A

They’re reversible so phosphatases used to do the reverse of the reaction

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11
Q

What happens to oxaloacetate?

A

Converted by phosphenolpyruvate carboxykinase to phosphenolpyruvate then converted to…

Fructose- 1,6,- bisphosphate converted to fructose 6-phosphate by fructose-1,6,- bisphosphotase

Glucose-6-phosphate converted to glucose by glucose 6 phosphatase

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12
Q

How can lactate be used to regenerate pyruvate?

A

Lactate can be taken up by the liver and utilised to regenerate pyruvate by lactate dehydrogenase (LDH) also known as the cori cycle

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13
Q

What non-carbohydrate precursors enter gluconeogenesis?

A

Lactate, amino acids, glycerol

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14
Q

Where are amino acids derived from?

A

Amino acids can be derived from diet or during times of starvation

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15
Q

What happens to triglycerides in gluconeogenesis?

A

Triglyceride hydrolysis yields fatty acids and glycerol.

glycerol backbone generates dihydroxyacetone phosphate (DHAP)

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16
Q

What is delta G for gluconeogeneis?

A

-38 KJ/mol

17
Q

What are ketogenic amino acids?

A

Give rise to skeletons which can’t enter gluconeogenesis but can be used for synthesis of ketone bodies and fatty acids

Fatty acids are converted into ketone bodies

18
Q

What occurs during levels of moderate exercise?

A

ATP demands met by oxidative phosphorylation using glucose or other substrates

Glucose transported from blood to muscle cells where it undergoes metabolism by glycolysis and TCA cycle to regenerate ATP by deoxidation of Co Factors

19
Q

How is increase in ATP demand for muscles met?

A

Increased number of glucose transporters on membrane of muscle cell

Adrenalin increases rate of glycolysis, increasing rate of gluconeogenesis in liver and increasing release of fatty acids from adipose

20
Q

What happens when demands for ATP by the muscle are not met?

A

Glycogen in muscle is broken down
To replenish NAD+ levels and maintain glycolysis, pyruvate is taken up by liver and converted into lactate by lactate dehydrogenase (LDH)
Lactate is then used in the liver to generate glucose by gluconeogenesis

21
Q

How can we measure the relative activities of enzymes in glycolysis?

A

Using Michaelis constant (Km)
We can measure the Km of hexokinase
Km of hexokinase I in muscle is around 0.1mM - operating at max velocity at all times
whereas in the liver hexokinase IV conc its 4mM

22
Q

What 4 hormones control blood glucose conc.?

A

Insulin- stores glucose as glycogen and fat
Glucagon- secreted when glucose conc. falls
Adrenalin- increases metabolic rate
Glucocorticoids- increase synthesis of metabolic enzymes in glucose availability

23
Q

What happens after a meal?

A

Increased glucose uptake by liver for glycogen synthesis
Increased uptake and glycogen synthesis in muscle
Increased triglyceride synthesis in adipose tissues
Increased usage of metabolic intermediates

24
Q

What happens when blood glucose levels begin to fall?

A

increased glucagon secretion from islets
Glucose production in liver from glycogen breakdown and gluconeogenesis
utilisation of fatty acid breakdown

25
Q

What happens after prolonged fasting?

A

Glucagon/insulin ratio increases further
Adipose tissue hydrolysis triglycerides to provide fatty acids
TCA cycle intermediates are reduced in amount to provide substrate for gluconeogenesis
Protein breakdown provides AAs for glujconeogeneis
Ketone bodies made from fatty acids in liver

26
Q

What is diabetes mellitus?

A

disorder of insulin release and signalling- imparted ability to regulate blood glucose conc.

Type I = inability to secrete enough insulin
Type II = insulin resistance

27
Q

Wha are complications of diabetes mellitus?

A

hyperglycaemia with progressive tissue damage
increase in plasma fatty acid and lipoprotein levels with possible cardiovascular complications
Increase in ketone bodied with risk of acidosis
Hypoglycaemia with consequent coma